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Selegiline (Eldepryl, Zelapar)

MAOI • Last reviewed 2025-09-27

General information

Oral selegiline is a selective MAO-B inhibitor used primarily for Parkinson disease but at higher doses provides antidepressant benefit when combined with dietary restrictions.

Metabolism produces amphetamine and methamphetamine derivatives that can cause insomnia, agitation, and increased blood pressure.

Patients require counseling on tyramine restrictions when using doses ≥10 mg/day or when combined with other serotonergic agents.

Therapeutic effects persist 1–2 weeks due to irreversible enzyme inhibition; washouts are required when switching therapies.

Dosing & administration

Depression (off-label): 5 mg twice daily tablets or 1.25–2.5 mg ODT once daily.

Avoid evening dosing to minimize insomnia; allow 14-day washout before/after serotonergic or adrenergic drugs.

Dose adjustments not required for mild hepatic/renal impairment but monitor closely.

Mechanism of action

Selectively inhibits MAO-B at low doses, increasing dopamine; higher doses inhibit MAO-A, augmenting serotonin and norepinephrine.

Metabolism & pharmacokinetics

Peak concentrations within 1 hour; half-life ~10 h though enzyme inhibition lasts longer. Metabolized via CYP2B6/CYP2C19/CYP3A4 to active metabolites excreted renally.

Drug interactions

Contraindicated with SSRIs, SNRIs, TCAs, bupropion, meperidine, tramadol, and dextromethorphan.

Sympathomimetics and stimulants increase hypertensive crisis risk.

Avoid tyramine-rich foods once doses reach 10 mg/day.

Monitoring & safety checks

  • Blood pressure and signs of hypertensive crisis

  • Sleep pattern, agitation

  • Medication list review for serotonergic agents

Discontinuation guidance

Taper over 1–2 weeks; maintain tyramine restrictions for 14 days after discontinuation.

References

  1. Selegiline Oral Prescribing Information — DailyMed
  2. Clinical management of oral MAOIs — Journal of Clinical Psychopharmacology (2022)
  3. CANMAT recommendations for oral MAOIs — Canadian Journal of Psychiatry (2024)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.